JP2000513929A - 進行性神経疾患を有するトランスジェニック非ヒト哺乳動物 - Google Patents
進行性神経疾患を有するトランスジェニック非ヒト哺乳動物Info
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- JP2000513929A JP2000513929A JP10503108A JP50310898A JP2000513929A JP 2000513929 A JP2000513929 A JP 2000513929A JP 10503108 A JP10503108 A JP 10503108A JP 50310898 A JP50310898 A JP 50310898A JP 2000513929 A JP2000513929 A JP 2000513929A
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- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
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- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| US08/664,872 | 1996-06-17 | ||
| US08/664,872 US5877399A (en) | 1994-01-27 | 1996-06-17 | Transgenic mice expressing APP-Swedish mutation develop progressive neurologic disease |
| PCT/US1997/010052 WO1997048792A1 (fr) | 1996-06-17 | 1997-06-17 | Mammiferes non humains transgeniques atteints de lesions neurologiques evolutives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2000513929A true JP2000513929A (ja) | 2000-10-24 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP10503108A Pending JP2000513929A (ja) | 1996-06-17 | 1997-06-17 | 進行性神経疾患を有するトランスジェニック非ヒト哺乳動物 |
Country Status (6)
| Country | Link |
|---|---|
| US (3) | US5877399A (fr) |
| EP (1) | EP0904349A4 (fr) |
| JP (1) | JP2000513929A (fr) |
| AU (1) | AU3481897A (fr) |
| CA (1) | CA2257852C (fr) |
| WO (1) | WO1997048792A1 (fr) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007534323A (ja) * | 2004-04-23 | 2007-11-29 | バック インスティチュート | アルツハイマー病のトランスジェニックモデル及び種々の神経変性疾患の治療におけるその使用 |
Families Citing this family (156)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO1995020666A2 (fr) * | 1994-01-27 | 1995-08-03 | Regents Of The University Of Minnesota | Mammiferes non humains transgeniques atteints de maladies neurologiques progressives |
| US5877399A (en) * | 1994-01-27 | 1999-03-02 | Johns Hopkins University | Transgenic mice expressing APP-Swedish mutation develop progressive neurologic disease |
| US6717031B2 (en) | 1995-06-07 | 2004-04-06 | Kate Dora Games | Method for selecting a transgenic mouse model of alzheimer's disease |
| US20010016951A1 (en) * | 1996-07-24 | 2001-08-23 | Bernd Sommer | Transgenic animal model for alzheimer disease |
| EP2305709A1 (fr) | 1997-04-09 | 2011-04-06 | Intellect Neurosciences, Inc. | Anticorps recombinants spécifiques à des fins bêta-amyloïdes, codage ADN et procédés d'utilisation associés |
| US6284944B1 (en) * | 1997-08-29 | 2001-09-04 | Cephalon, Inc, | Gene-targeted non-human mammal with a human fad presenilin mutation and generational offspring |
| US7790856B2 (en) * | 1998-04-07 | 2010-09-07 | Janssen Alzheimer Immunotherapy | Humanized antibodies that recognize beta amyloid peptide |
| US7964192B1 (en) | 1997-12-02 | 2011-06-21 | Janssen Alzheimer Immunotherapy | Prevention and treatment of amyloidgenic disease |
| US6743427B1 (en) | 1997-12-02 | 2004-06-01 | Neuralab Limited | Prevention and treatment of amyloidogenic disease |
| TWI239847B (en) * | 1997-12-02 | 2005-09-21 | Elan Pharm Inc | N-terminal fragment of Abeta peptide and an adjuvant for preventing and treating amyloidogenic disease |
| US6750324B1 (en) | 1997-12-02 | 2004-06-15 | Neuralab Limited | Humanized and chimeric N-terminal amyloid beta-antibodies |
| US20080050367A1 (en) * | 1998-04-07 | 2008-02-28 | Guriq Basi | Humanized antibodies that recognize beta amyloid peptide |
| US6787523B1 (en) | 1997-12-02 | 2004-09-07 | Neuralab Limited | Prevention and treatment of amyloidogenic disease |
| US7179892B2 (en) * | 2000-12-06 | 2007-02-20 | Neuralab Limited | Humanized antibodies that recognize beta amyloid peptide |
| US7588766B1 (en) | 2000-05-26 | 2009-09-15 | Elan Pharma International Limited | Treatment of amyloidogenic disease |
| US6913745B1 (en) | 1997-12-02 | 2005-07-05 | Neuralab Limited | Passive immunization of Alzheimer's disease |
| US6710226B1 (en) | 1997-12-02 | 2004-03-23 | Neuralab Limited | Transgenic mouse assay to determine the effect of Aβ antibodies and Aβ Fragments on alzheimer's disease characteristics |
| US6761888B1 (en) * | 2000-05-26 | 2004-07-13 | Neuralab Limited | Passive immunization treatment of Alzheimer's disease |
| US6923964B1 (en) | 1997-12-02 | 2005-08-02 | Neuralab Limited | Active immunization of AScr for prion disorders |
| PT1049767E (pt) * | 1998-01-08 | 2005-10-31 | Agronomique Inst Nat Rech | Coelho transgenico que expressa uma lipoproteina (a) humana funcional |
| JP4290329B2 (ja) * | 1998-01-08 | 2009-07-01 | 第一三共株式会社 | 遺伝子変異動物 |
| US6664443B1 (en) | 1998-05-01 | 2003-12-16 | Mayo Foundation For Medical Education And Research | Pathogenic Tau mutations in transgenic mice |
| CA2330944A1 (fr) | 1998-05-01 | 1999-11-11 | Mayo Foundation For Medical Education And Research | Mutations tau pathogenes |
| US20030147882A1 (en) * | 1998-05-21 | 2003-08-07 | Alan Solomon | Methods for amyloid removal using anti-amyloid antibodies |
| US6518011B1 (en) * | 1999-01-13 | 2003-02-11 | Bristol-Myers Squibb Company | Method for screening compounds to identify beta-amyloid production modulators |
| JP2001017028A (ja) * | 1999-05-06 | 2001-01-23 | Mitsubishi Chemicals Corp | アポｅヒト化哺乳動物 |
| WO2000071671A2 (fr) | 1999-05-26 | 2000-11-30 | New York University | Nouveaux genes mutants dans la demence familiale britannique et la demence familiale danoise |
| US6787637B1 (en) | 1999-05-28 | 2004-09-07 | Neuralab Limited | N-Terminal amyloid-β antibodies |
| UA81216C2 (en) * | 1999-06-01 | 2007-12-25 | Prevention and treatment of amyloid disease | |
| US6610905B1 (en) | 1999-07-21 | 2003-08-26 | Schering Corporation | Transgenic mouse model for Kaposi's sarcoma |
| US7273964B1 (en) | 1999-08-06 | 2007-09-25 | Scuola Internazionale Superiore Di Studi Avanzati | Non-human transgenic animals for the study of neurodegenerative syndromes |
| DE60124080T2 (de) * | 2000-03-23 | 2007-03-01 | Elan Pharmaceuticals, Inc., San Francisco | Verbindungen und verfahren zur behandlung der alzheimerschen krankheit |
| US6992081B2 (en) | 2000-03-23 | 2006-01-31 | Elan Pharmaceuticals, Inc. | Compounds to treat Alzheimer's disease |
| MXPA02009756A (es) * | 2000-04-03 | 2003-06-17 | Bristol Myers Squibb Co | Aislamiento de complejo de proteina de gamma-secretasa funcionalmente activa y metodos de deteccion de la actividad e inhibidores de la misma. |
| DE60144164D1 (de) | 2000-06-20 | 2011-04-14 | Univ Toronto | Transgenes Tiermodel für neurodegenerative Krankheiten |
| US7371920B2 (en) * | 2000-06-20 | 2008-05-13 | The Governing Council Of The University Of Toronto | Transgenic mouse model of neurodegenerative disorders |
| EP1666452A2 (fr) | 2000-06-30 | 2006-06-07 | Elan Pharmaceuticals, Inc. | Composés pour le traitement de la maladie d'Alzheimer |
| PE20020276A1 (es) | 2000-06-30 | 2002-04-06 | Elan Pharm Inc | COMPUESTOS DE AMINA SUSTITUIDA COMO INHIBIDORES DE ß-SECRETASA PARA EL TRATAMIENTO DE ALZHEIMER |
| US6846813B2 (en) * | 2000-06-30 | 2005-01-25 | Pharmacia & Upjohn Company | Compounds to treat alzheimer's disease |
| ES2248356T3 (es) | 2000-06-30 | 2006-03-16 | Elan Pharmaceuticals, Inc. | Compuestos para tratar la enfermedad de alzheimer. |
| US20030096864A1 (en) * | 2000-06-30 | 2003-05-22 | Fang Lawrence Y. | Compounds to treat alzheimer's disease |
| US7186521B2 (en) * | 2000-09-25 | 2007-03-06 | The Regents Of The University Of California | Determining the effect of a substance on sequestration, uptake, and accumulation of amyloid in brain cells |
| US7700751B2 (en) | 2000-12-06 | 2010-04-20 | Janssen Alzheimer Immunotherapy | Humanized antibodies that recognize β-amyloid peptide |
| PE20020574A1 (es) * | 2000-12-06 | 2002-07-02 | Wyeth Corp | Anticuerpos humanizados que reconocen el peptido amiloideo beta |
| EP1764734A1 (fr) * | 2001-02-22 | 2007-03-21 | Sony Corporation | Système de fourniture et d'acquisition de contenus |
| EP1395551B1 (fr) * | 2001-06-01 | 2008-05-21 | Elan Pharmaceuticals, Inc. | Derives d'hydroxyalkylamines comme inhibiteurs de la beta-secretase et leur utilisation pour le traitement de la maladie d'alzheimer ou de maladies similaires |
| JP2004532894A (ja) | 2001-06-13 | 2004-10-28 | イーラン ファーマスーティカルズ、インコーポレイテッド | アルツハイマー病を治療するためのアミンジオール |
| BR0210721A (pt) * | 2001-06-27 | 2004-07-20 | Elan Pharm Inc | Composto, sal ou éster farmaceuticamente aceitável, método para fabricar um composto, e, método para tratar um paciente que tem, ou para evitar que o paciente adquira uma doença ou condição |
| US20070213407A1 (en) * | 2001-06-29 | 2007-09-13 | Elan Pharmaceuticals And Pharmacia & Upjohn Company Llc | Compounds to treat Alzheimer's disease |
| AU2002315494A1 (en) * | 2001-06-29 | 2003-03-03 | Mayo Foundation For Medical Education And Research | Bri constructs and methods of using |
| BR0211118A (pt) * | 2001-07-10 | 2004-10-26 | Elan Pharm Inc | Composto, métodos para o tratamento ou prevenção de doenças e para fabricar um composto, intermediário, e, uso de um composto ou sal |
| US7053109B2 (en) * | 2001-07-10 | 2006-05-30 | Pharmacia & Upjohn Company | Aminediols for the treatment of Alzheimer's disease |
| US7297553B2 (en) * | 2002-05-28 | 2007-11-20 | Nanosphere, Inc. | Method for attachment of silylated molecules to glass surfaces |
| CA2462851A1 (fr) | 2001-10-04 | 2003-04-10 | Elan Pharmaceuticals, Inc. | Hydroxypropylamines |
| NZ533107A (en) * | 2001-11-08 | 2007-04-27 | Upjohn Co | N, N'-substituted-1,3-diamino-2-hydroxypropane derivatives |
| US7479579B2 (en) * | 2001-12-20 | 2009-01-20 | The Regents Of The University Of California | Triple transgenic mouse model of Alzheimer's disease |
| WO2003057165A2 (fr) | 2002-01-04 | 2003-07-17 | The Rockefeller University | Compositions et procedes de prevention et de traitement de troubles lies au peptide beta-amyloide |
| US20040016008A1 (en) * | 2002-01-07 | 2004-01-22 | Brimijoin William Stephen | Hybrid transgenic mouse with accelerated onsent of Alzheimer type amyloid plaques in brain |
| JP2005518791A (ja) * | 2002-02-27 | 2005-06-30 | ファルマシア アンド アップジョン カンパニー リミティド ライアビリティー カンパニー | Ｉｍｒ−３２細胞からのアミロイド−ベータペプチドの高レベル生産 |
| MY139983A (en) * | 2002-03-12 | 2009-11-30 | Janssen Alzheimer Immunotherap | Humanized antibodies that recognize beta amyloid peptide |
| AU2003303141A1 (en) * | 2002-04-30 | 2004-07-22 | Elan Pharmaceuticals, Inc. | Hydroxypropyl amides for the treatment of alzheimer's disease |
| UY27967A1 (es) * | 2002-09-10 | 2004-05-31 | Pfizer | Acetil 2-hindroxi-1,3-diaminoalcanos |
| BR0316629A (pt) * | 2002-11-27 | 2005-10-11 | Elan Pharm Inc | Uréias e carbamatos substituìdos |
| DE10303974A1 (de) | 2003-01-31 | 2004-08-05 | Abbott Gmbh & Co. Kg | Amyloid-β(1-42)-Oligomere, Verfahren zu deren Herstellung und deren Verwendung |
| JP2006516639A (ja) * | 2003-02-01 | 2006-07-06 | ニユーララブ・リミテツド | 可溶性Ａ−βに対する抗体を生成させるための能動免疫 |
| US7341847B2 (en) * | 2003-04-02 | 2008-03-11 | Agency For Science, Technology And Research | Promoter construct for gene expression in neuronal cells |
| BRPI0409627A (pt) * | 2003-04-21 | 2006-04-25 | Elan Pharm Inc | 2-hidróxi-3-diaminoalcanos de fenacila |
| AR044044A1 (es) * | 2003-04-21 | 2005-08-24 | Elan Pharm Inc | 2-hidroxi-3-diaminoalcanos de benzamida |
| PE20050627A1 (es) | 2003-05-30 | 2005-08-10 | Wyeth Corp | Anticuerpos humanizados que reconocen el peptido beta amiloideo |
| JP2007522129A (ja) * | 2004-01-21 | 2007-08-09 | エラン ファーマシューティカルズ，インコーポレイテッド | アスパラギン酸プロテアーゼ阻害薬を用いるアミロイドーシスの処置方法 |
| EP1734961A2 (fr) * | 2004-03-09 | 2006-12-27 | Elan Pharmaceuticals, Inc. | Procedes de traitement de l'amylose mettant en oeuvre des inhibiteurs de la protease a base d'aspartyle bicyclique |
| EP1734942A1 (fr) | 2004-03-09 | 2006-12-27 | Elan Pharmaceuticals, Inc. | Uree et carbamate substitues, phenacyl-2-hydroxy-3-diaminoalcane, et benzamide-2-hydroxy-3-diaminoalcane inhibiteurs d'aspartyl-protease |
| CA2558034A1 (fr) * | 2004-03-09 | 2005-09-22 | Elan Pharmaceuticals, Inc. | Aspartyle a base d'hydroxyethylamine substitue inhibiteurs de la protease |
| WO2005087752A2 (fr) * | 2004-03-09 | 2005-09-22 | Elan Pharmaceuticals, Inc. | Aspartyle a base d'hydroxyethylamine inhibiteurs de la protease |
| SE0400707D0 (sv) | 2004-03-22 | 2004-03-22 | Bioarctic Neuroscience Ab | Transgenic animal model |
| EP1750719A2 (fr) * | 2004-05-19 | 2007-02-14 | Boehringer Ingelheim International GmbH | Procede pour traiter des maladies et des etats associes a un niveau modifie de peptides beta amyloides et nouveaux composes d'enolcarboxamide |
| CA2572775A1 (fr) * | 2004-07-09 | 2006-01-26 | Elan Pharmaceuticals, Inc. | Inhibiteurs d'aspartyl-protease d'hydroxyethylamine derivee des oximes |
| CA2573138A1 (fr) * | 2004-07-09 | 2006-01-26 | Elan Pharmaceuticals Inc. | Inhibiteurs d'une aspartyl protease de type hydroxyethylamine substituee par un derive d'oxime |
| CA2488113A1 (fr) * | 2004-11-18 | 2006-05-18 | Jean Michel Heard | Modele animal non humain de la maladie d'alzheimer et utilisations connexes |
| US8383637B2 (en) * | 2004-08-06 | 2013-02-26 | Jansssen Pharmaceutica N.V. | 2-amino-quinazoline derivatives useful as inhibitors of β-secretase (BACE) |
| US8426429B2 (en) * | 2004-08-06 | 2013-04-23 | Jansssen Pharmaceutica N.V. | 2-amino-quinazoline derivatives useful as inhibitors of β-secretase (BACE) |
| US8436006B2 (en) * | 2004-08-06 | 2013-05-07 | Jansssen Pharmaceutica N.V. | 2-amino-quinazoline derivatives useful as inhibitors of β-secretase (BACE) |
| EP1802574A2 (fr) * | 2004-08-27 | 2007-07-04 | Elan Pharmaceuticals Inc. | Methodes de traitement de l'amyloidose au moyen d'inhibiteurs d'aspartyle protease d'ethanolamine cyclique |
| AU2005304931A1 (en) * | 2004-11-05 | 2006-05-18 | Wyeth | Pet and magnetic resonance for screening Alzheimer's disease therapeutics |
| PE20061329A1 (es) * | 2004-12-15 | 2006-12-08 | Neuralab Ltd | Anticuerpos ab humanizados para mejorar la cognicion |
| WO2006066049A2 (fr) * | 2004-12-15 | 2006-06-22 | Neuralab Limited | Anticorps humanises reconnaissant le peptide beta amyloide |
| JP2008524247A (ja) * | 2004-12-15 | 2008-07-10 | エラン ファーマ インターナショナル リミテッド | 認知の改善における使用のためのアミロイドβ抗体 |
| WO2006069697A1 (fr) * | 2004-12-30 | 2006-07-06 | F. Hoffmann-La Roche Ag | Evaluation par colorimetrie des caracteristiques des peptides |
| AU2006214179A1 (en) | 2005-02-17 | 2006-08-24 | Biogen Idec Ma Inc. | Treating neurological disorders |
| US20060272038A1 (en) * | 2005-05-27 | 2006-11-30 | Michael De Vivo | Transgenic Alzheimer's mouse model vectors and uses thereof |
| EP1746092A1 (fr) | 2005-07-22 | 2007-01-24 | Exonhit Therapeutics SA | Composés et méthodes pour le traitment des maladies relatives aux peptides beta-amyloides |
| US20080293680A1 (en) * | 2005-08-03 | 2008-11-27 | Stefan Peters | Substituted Ethane-1,2-Diamines for the Treatment of Alzheimer's Disease II |
| US20090042867A1 (en) * | 2005-08-11 | 2009-02-12 | Klaus Fuchs | Compounds for the treatment of alzheimer's disease |
| CA2618474A1 (fr) * | 2005-08-11 | 2007-02-15 | Boehringer Ingelheim International Gmbh | Composes pour le traitement de la maladie d'alzheimer |
| WO2007017507A1 (fr) * | 2005-08-11 | 2007-02-15 | Boehringer Ingelheim International Gmbh | Inhibiteurs de la beta-secretase pour traiter la maladie d'alzheimer |
| JP2009504614A (ja) * | 2005-08-11 | 2009-02-05 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | アルツハイマー病の治療用化合物 |
| JP2009511589A (ja) * | 2005-10-12 | 2009-03-19 | エラン ファーマシューティカルズ，インコーポレイテッド | アリール−シクロプロピル誘導体のアスパルチルプロテアーゼ阻害剤を使用してアミロイドーシスを治療する方法 |
| WO2007047305A1 (fr) * | 2005-10-12 | 2007-04-26 | Elan Pharmaceuticals, Inc. | Procedes de traitement de l'amyloïdose en utilisant des derives de cyclopropyle inhibiteurs de l'aspartyle-protease |
| PL1976877T5 (pl) | 2005-11-30 | 2017-09-29 | Abbvie Inc | Przeciwciała monoklonalne przeciwko białku amyloidu beta oraz ich zastosowania |
| CN117903302A (zh) | 2005-11-30 | 2024-04-19 | Abbvie 公司 | 抗-Aβ球聚体抗体，其相关产品，生产所述抗体的方法，所述抗体的应用以及使用方法 |
| ES2409844T3 (es) * | 2006-01-30 | 2013-06-28 | Grifols Therapeutics Inc. | Metodo para el tratamiento y la profilaxis de enfermedades relacionadas con la deposicion de amiloide utilizando IgM |
| US7776882B2 (en) * | 2006-02-06 | 2010-08-17 | Baxter Ellen W | 2-amino-3,4-dihydro-quinoline derivatives useful as inhibitors of β-secretase (BACE) |
| US7932261B2 (en) * | 2006-02-06 | 2011-04-26 | Janssen Pharmaceutica Nv | Macrocycle derivatives useful as inhibitors of β-secretase (BACE) |
| US7868022B2 (en) * | 2006-02-06 | 2011-01-11 | Janssen Pharmaceutica Nv | 2-amino-quinoline derivatives useful as inhibitors of β-secretase (BACE) |
| TW200808751A (en) * | 2006-04-13 | 2008-02-16 | Astrazeneca Ab | New compounds |
| US8784810B2 (en) * | 2006-04-18 | 2014-07-22 | Janssen Alzheimer Immunotherapy | Treatment of amyloidogenic diseases |
| SI1849762T1 (sl) * | 2006-04-21 | 2009-12-31 | Cellzome Ltd | Substituirane bifenil karboksilne kisline in derivati le-teh |
| EP2687223B1 (fr) | 2006-05-30 | 2017-07-12 | Mayo Foundation For Medical Education And Research | Detection et traitement de la démence |
| EP2037948B1 (fr) | 2006-05-30 | 2016-04-13 | Mayo Foundation For Medical Education And Research | Detection et traitement de la demence |
| TW200815349A (en) * | 2006-06-22 | 2008-04-01 | Astrazeneca Ab | New compounds |
| JP2010500039A (ja) * | 2006-08-10 | 2010-01-07 | ザ ボード オブ トラスティーズ オブ ザ レランド スタンフォード ジュニア ユニバーシティー | 細胞の示差的標識 |
| CA2666246C (fr) | 2006-10-12 | 2013-12-31 | Bellus Health (International) Limited | Procedes, composes, compositions et vehicules permettant de delivrer l'acide 3-amino-1-propane sulfonique |
| US8455626B2 (en) | 2006-11-30 | 2013-06-04 | Abbott Laboratories | Aβ conformer selective anti-aβ globulomer monoclonal antibodies |
| EP2486928A1 (fr) | 2007-02-27 | 2012-08-15 | Abbott GmbH & Co. KG | Procédé pour le traitement des amyloses |
| US8575120B2 (en) | 2007-03-13 | 2013-11-05 | The Children's Hospital Of Philadelphia | Genetic alterations on chromosome 12 and methods of use thereof for the diagnosis and treatment of type 1 diabetes |
| US8003097B2 (en) * | 2007-04-18 | 2011-08-23 | Janssen Alzheimer Immunotherapy | Treatment of cerebral amyloid angiopathy |
| CA2684323A1 (fr) * | 2007-04-18 | 2008-10-30 | Janssen Alzheimer Immunotherapy | Prevention et traitement d'angiopathie amyloide cerebrale |
| JP2010527375A (ja) * | 2007-05-15 | 2010-08-12 | ヘリコン セラピューティクス，インコーポレイテッド | Ｇｐｒ１２の阻害による認知障害の治療方法 |
| JP5450407B2 (ja) | 2007-07-06 | 2014-03-26 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 置換アミノ−キナゾリノン、前記化合物を含む薬物、それらの使用及び製造方法 |
| PL2182983T3 (pl) | 2007-07-27 | 2014-10-31 | Janssen Alzheimer Immunotherap | Leczenie chorób amyloidowych z wykorzystaniem humanizowanych przeciwciał specyficznych względem Abeta |
| JP5049713B2 (ja) * | 2007-09-14 | 2012-10-17 | 株式会社コナミデジタルエンタテインメント | ゲームシステム並びにこれを構成するゲーム装置及び課題報知装置 |
| JO3076B1 (ar) * | 2007-10-17 | 2017-03-15 | Janssen Alzheimer Immunotherap | نظم العلاج المناعي المعتمد على حالة apoe |
| AU2008312771B2 (en) * | 2007-10-17 | 2012-11-01 | Janssen Pharmaceutica, N.V. | Biphenyl carboxylic acids and derivatives thereof |
| AU2008312612B2 (en) * | 2007-10-19 | 2013-11-28 | Janssen Pharmaceutica, N.V. | Piperidinyl and piperazinyl modulators of gamma-secretase |
| US7951843B2 (en) * | 2007-10-19 | 2011-05-31 | Janssen Pharmaceutica N.V. | Amide linked modulators of γ-secretase |
| AU2008312362A1 (en) * | 2007-10-19 | 2009-04-23 | Janssen Pharmaceutica, N.V. | Gsm intermediates |
| AU2008312355B2 (en) * | 2007-10-19 | 2013-07-04 | Janssen Pharmaceutica, N.V. | Carbon linked modulators of y-secretase |
| WO2009052350A1 (fr) * | 2007-10-19 | 2009-04-23 | Janssen Pharmaceutica, N.V. | Modulateurs de la g-secrétase liés à une amine |
| CA2713998A1 (fr) * | 2008-01-28 | 2009-08-06 | Janssen Pharmaceutica N.V. | Derives de quinoline 6-substituee-thio-2-amino-quinoline utiles en tant qu'inhibiteurs de la .beta.-secretase (bace) |
| TW200936156A (en) | 2008-01-28 | 2009-09-01 | Novartis Ag | Methods and compositions using Klotho-FGF fusion polypeptides |
| US8420088B2 (en) | 2008-01-28 | 2013-04-16 | Novartis Ag | Methods and compositions using FGF23 fusion polypeptides |
| WO2009097401A1 (fr) * | 2008-01-29 | 2009-08-06 | Janssen Pharmaceutica N.V. | DÉRIVÉS DE 2-AMINO-QUINOLINE UTILISÉS COMME INHIBITEURS DE LA β-SÉCRÉTASE (BACE) |
| SI2257643T1 (sl) | 2008-02-19 | 2018-12-31 | The Children's Hospital Of Philadelphia | Identifikacija predelov vnetne črevesne bolezni z začetkom v otroštvu in metode za njeno uporabo za diagnozo in zdravljenje te bolezni |
| AU2009246134B2 (en) | 2008-05-16 | 2016-03-03 | The Children's Hospital Of Philadelphia | Genetic alterations on chromosomes 21q, 6q and 15q and methods of use thereof for the diagnosis and treatment of type I diabetes |
| US8933295B2 (en) | 2008-06-20 | 2015-01-13 | Janssen Biotech, Inc. | Identifying agents to treat alzheimer's disease-related decreased sorting behavior by administration to a triple transgenic mouse expressing mutant forms of APP, presenilin or tau |
| US9067981B1 (en) | 2008-10-30 | 2015-06-30 | Janssen Sciences Ireland Uc | Hybrid amyloid-beta antibodies |
| WO2010056194A1 (fr) * | 2008-11-14 | 2010-05-20 | Astrazeneca Ab | Dérivés de 5h-pyrrolo [ 3, 4-b] pyridine et leur utilisation |
| TW201020244A (en) * | 2008-11-14 | 2010-06-01 | Astrazeneca Ab | New compounds |
| WO2010056195A1 (fr) * | 2008-11-14 | 2010-05-20 | Astrazeneca Ab | Nouveaux composés 575 |
| US20110023152A1 (en) * | 2008-12-04 | 2011-01-27 | Sigma-Aldrich Co. | Genome editing of cognition related genes in animals |
| US8008539B1 (en) | 2009-03-19 | 2011-08-30 | University Of South Florida | Generation of transgenic human soluble amyloid precursor protein alpha expressing mice |
| US8871460B2 (en) | 2009-11-09 | 2014-10-28 | Neurogenetic Pharmaceuticals, Inc. | Gamma-secretase modulatory compounds, methods for identifying same, and uses therefor |
| CA2796339C (fr) | 2010-04-15 | 2020-03-31 | Abbott Laboratories | Proteines de liaison a la beta amyloide |
| CA2808187A1 (fr) | 2010-08-14 | 2012-02-23 | Abbvie Inc. | Proteines de liaison beta-amyloides |
| BR112013003847A8 (pt) | 2010-08-19 | 2017-12-26 | Buck Institute For Age Res | métodos de tratar a deterioração cognitiva moderada (mci) e os distúrbios relacionados |
| WO2013027191A1 (fr) | 2011-08-25 | 2013-02-28 | Novartis Ag | Procédés et compositions utilisant des polypeptides de fusion fgf23 |
| JP5605718B2 (ja) * | 2012-01-23 | 2014-10-15 | 独立行政法人理化学研究所 | アルツハイマー病モデル動物およびその用途 |
| WO2013142370A1 (fr) | 2012-03-19 | 2013-09-26 | Varghese John | Inhibiteurs de bace spécifiques de l'app (asbi) et leurs utilisations |
| US10202355B2 (en) | 2013-02-12 | 2019-02-12 | Buck Institute For Research On Aging | Hydantoins that modulate bace-mediated app processing |
| EP3212811B1 (fr) | 2014-10-29 | 2020-09-09 | The Children's Hospital of Philadelphia | Diagnostic de modifications génétiques associées à l'oesophagite éosinophilique |
| WO2016088059A1 (fr) | 2014-12-04 | 2016-06-09 | Novartis Ag | Procédés et compositions employant des polypeptides variants de klotho |
| US20180161395A1 (en) * | 2015-06-12 | 2018-06-14 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Methods and pharmaceutical composition for the treatment of alzheimer's disease |
| JP2018523488A (ja) | 2015-08-21 | 2018-08-23 | ザ・チルドレンズ・ホスピタル・オブ・フィラデルフィアＴｈｅ Ｃｈｉｌｄｒｅｎ’Ｓ Ｈｏｓｐｉｔａｌ Ｏｆ Ｐｈｉｌａｄｅｌｐｈｉａ | 自己免疫疾患の治療及び診断のために組み合わせて使用するための組成物及び方法 |
| AU2016311502B2 (en) | 2015-08-27 | 2019-07-18 | Nantneuro, Llc | Compositions for app-selective bace inhibition and uses therfor |
| IL262957B2 (en) | 2016-05-12 | 2024-04-01 | Buck Inst Res Aging | 6-Fluorotropistrone and a pharmaceutical formulation comprising it for the relief of amyloid-related diseases |
| US20240065237A1 (en) * | 2020-12-16 | 2024-02-29 | The Jackson Laboratory | A genetically modified immunodeficient mouse expressing human or humanized app and mutated human psen1 |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4873191A (en) * | 1981-06-12 | 1989-10-10 | Ohio University | Genetic transformation of zygotes |
| AU3056289A (en) * | 1988-01-13 | 1989-08-11 | Mclean Hospital Corporation, The | Genetic constructs containing the alzheimer brain amyloid gene |
| EP0451700A1 (fr) * | 1990-04-10 | 1991-10-16 | Miles Inc. | Minigènes APP recombinants pour l'expression dans des souris transgéniques comme modèles de la maladie d'Alzheimer |
| ES2217250T3 (es) * | 1990-06-15 | 2004-11-01 | Scios Inc. | Mamifero transgenico, no humano que muestra la patologia de formacion amiloides de la enfermedad de alzheimer. |
| AU8768191A (en) * | 1990-09-28 | 1992-04-28 | Upjohn Company, The | Transgenic animals with alzheimer's amyloid precursor gene |
| ES2236682T5 (es) * | 1991-01-21 | 2011-03-31 | Elan Pharmaceuticals, Inc. | Ensayo y modelo para la enfermedad de alzheimer. |
| US5672805A (en) * | 1991-07-18 | 1997-09-30 | The Regents Of The University Of California | Transgenic mice expressing the neurotoxic C-terminus of β-amyloid precursor protein |
| ES2204899T3 (es) * | 1992-01-07 | 2004-05-01 | Elan Pharmaceuticals, Inc. | Modelos de animales transgenicos para la enfermedad de alzheimer. |
| US5604102A (en) * | 1992-04-15 | 1997-02-18 | Athena Neurosciences, Inc. | Methods of screening for β-amyloid peptide production inhibitors |
| US5455169A (en) * | 1992-06-04 | 1995-10-03 | Alzheimer's Institute Of America, Inc. | Nucleic acids for diagnosing and modeling Alzheimer's disease |
| ATE198622T1 (de) * | 1993-10-27 | 2001-01-15 | Elan Pharm Inc | Transgene tiere, die app allele mit der schwedischen mutation beherbergen |
| JPH07132033A (ja) * | 1993-11-12 | 1995-05-23 | Hoechst Japan Ltd | アルツハイマー病モデルトランスジェニック動物 |
| WO1995020666A2 (fr) * | 1994-01-27 | 1995-08-03 | Regents Of The University Of Minnesota | Mammiferes non humains transgeniques atteints de maladies neurologiques progressives |
| US5877399A (en) * | 1994-01-27 | 1999-03-02 | Johns Hopkins University | Transgenic mice expressing APP-Swedish mutation develop progressive neurologic disease |
-
1996
- 1996-06-17 US US08/664,872 patent/US5877399A/en not_active Expired - Lifetime
-
1997
- 1997-06-17 EP EP97931096A patent/EP0904349A4/fr not_active Withdrawn
- 1997-06-17 JP JP10503108A patent/JP2000513929A/ja active Pending
- 1997-06-17 CA CA2257852A patent/CA2257852C/fr not_active Expired - Lifetime
- 1997-06-17 WO PCT/US1997/010052 patent/WO1997048792A1/fr not_active Application Discontinuation
- 1997-06-17 AU AU34818/97A patent/AU3481897A/en not_active Abandoned
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1999
- 1999-03-02 US US09/260,897 patent/US6509515B2/en not_active Expired - Fee Related
-
2002
- 2002-10-15 US US10/271,314 patent/US20030229907A1/en not_active Abandoned
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007534323A (ja) * | 2004-04-23 | 2007-11-29 | バック インスティチュート | アルツハイマー病のトランスジェニックモデル及び種々の神経変性疾患の治療におけるその使用 |
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| EP0904349A4 (fr) | 2002-09-25 |
| CA2257852A1 (fr) | 1997-12-24 |
| CA2257852C (fr) | 2010-02-23 |
| WO1997048792A1 (fr) | 1997-12-24 |
| US20020019992A1 (en) | 2002-02-14 |
| US20030229907A1 (en) | 2003-12-11 |
| US6509515B2 (en) | 2003-01-21 |
| AU3481897A (en) | 1998-01-07 |
| US5877399A (en) | 1999-03-02 |
| EP0904349A1 (fr) | 1999-03-31 |
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